|Detection of LRIG3 in KATO‑III Human Cell Line by Flow Cytometry. KATO‑III human gastric carcinoma cell line was stained with Mouse Anti-Human LRIG3 APC‑conjugated Monoclonal Antibody (Catalog # FAB3495A, filled histogram) or isotype control antibody (Catalog # IC0041A, open histogram). View our protocol for Staining Membrane-associated Proteins.|
LRIG3 (Leucine-rich Repeats and Ig-like domains-3) is an approximately 140 kDa type I transmembrane glycoprotein member of the mammalian LRIG glycoprotein family. This family contains three members who share 45-50% amino acid (aa) sequence identity (1). All members contain at least fifteen LRRs, accompanied by two flanking cysteine-rich regions and three C2-type Ig-like domains in their extracellular domains (ECD) (1). LRIG3 mRNA is widely expressed, with highest levels in stomach, skin, thyroid and small intestine (1). Human LRIG3 is synthesized as a 1119 amino acid (aa) precursor. It contains a 24 aa signal sequence, a 785 aa ECD, a 21 aa transmembrane sequence, and a 289 aa intracellular region. One splice variant exists that has a 19 aa substitution for the first 79 aa of the standard (or long) form. This substitution appears to encode an alternate signal sequence, resulting in a mature protein that lacks the first and part of the second LRR. LRIG1, a related family member, is known to bind the EGF family receptors ErbB1-4, via either its LRR or Ig-like domains. It also binds the ubiquitin ligase, c-Cbl, and promotes ubiquitination, internalization and destruction of these receptors (2, 3). LRIG3, by contrast, would appear to oppose LRIG1 activity, in particular by promoting the expression of ErbB1-4. LRIG1, in kind, downregulates LRIG3 activity by inducing its proteolytic degradation (4). Within the cell, LRIG3 is expressed in the perinuclear region as well as on the cell surface. Perinuclear location of LRIG3 in grade III and IV astrocytic tumors has been associated with better patient survival (5). Human LRIG3 ECD shares 91%, 92%, 95% and 98% aa sequence identity with mouse, rat, bovine and canine LRIG3 ECD, respectively.